Key Features of the Interaction Between Malaria and its Surrounding Environments

Key Features of the Interaction Between Malaria and its Surrounding Environments

INTERACTION BETWEEN DIFFERENT Plasmodium SPECIES AND STRAINS

In an individual infected with multiple Plasmodium species or strains, the different species and/or strains interact with each other in a manner that is inhibits the excessive growth of the total Plasmodium population. Bruce et al (2000) explained that this interaction is a form of density dependent regulation of the rate of population growth. It was proposed that the density dependent regulation comes into action when the Plasmodium population density exceeds a threshold. The regulation is not species or strain specific, meaning that the growth of all Plasmodium species and strains in a population are inhibited. This allows the host’s immune response to target and kill the different Plasmodium species, thus reducing the density of the total population. Once the population density falls below the threshold, the density dependent regulation mechanism is inactivated and Plasmodium growth is no longer inhibited. Consequently, all Plasmodium strains and species will grow, where any one of them can become the new dominant species or strain. 

INTERACTION BETWEEN Plasmodium AND THE HOST’S IMMUNE SYSTEM 

The immune system of humans will often recognise Plasmodium as foreign, and therefore activate an immune response against the pathogen. Yilmaz et al (2014) investigated the ability of anti-α-gal antibodies in targeting Plasmodium sporozoites for degradation via the complement pathway of the immune system. As the name suggests, α-gal antibodies target the α-gal glycan on the surface of Plasmodium sporozoites. By binding to the sporozoites, the antibodies activate the classical complement system to recruit leukocytes, such as neutrophils and monocytes. These white blood cells destroy the sporozoites and prevent them from infecting the liver and red blood cells. Hence, α-gal antibodies and the complement system protect an uninfected individual from malaria. Interestingly, Plasmodium can inhibit class switching in antibodies. Class switching is a process involved in the maturation of the antibody response. Hence, Plasmodium sporozoites can respond to the human immune system by hindering it to promote its own ability to infect humans.

In addition to α-gal antigens, the human immune system can produce antibodies that target other Plasmodium antigens such as PfEMP1. This antigen is encoded by the var gene, which are present in multiple copies within a single Plasmodium organism. Although only one copy is expressed at a given time, Plasmodium can change the copy which it expresses, giving rise to antigenic variation (Petter and Duffy 2015). Hence, Plasmodium can respond to antibodies targeting a specific PfEMP1 by changing the var gene which it expresses. By doing so, the Plasmodium expresses a different PfEMP1 which would not be initially recognised by the host’s immune system. Thus, this enables Plasmodium to evade the host’s immune system.  

INTERACTION BETWEEN Plasmodium AND THE MOSQUITO MICROBIOME

The mosquito microbiome can prevent Plasmodium species from infecting the mosquito. For example, Plasmodium is required to colonise of the mosquito’s gut in order to infect the mosquito. However, certain species in the mosquito gut microbiota can hinder Plasmodium species from colonising the mosquito gut, and does so irrespective of the Plasmodium species. One mechanism that the mosquito gut microbiota induces colonisation resistance against Plasmodium is through the production of metabolites with antimicrobial activity against Plasmodium species. Some of these metabolites include reactive oxygen species to inhibit Plasmodium growth, or toxins that can kill Plasmodium species. The mosquito gut microbiota can also induce colonisation resistance in mosquitoes by activating the mosquito’s immune system, such as the Imd (immune deficiency) pathway. This pathway activates a protein, called TEP1, which has anti-Plasmodium activity (Romoli and Gendrin, 2018). Interestingly, the gut microbiota can also induce the expression of PGRPLB which dampens the Imd immune response therefore potentially promote Plasmodium colonisation in mosquitoes. Nonetheless, Romoli and Gendrin (2018) concluded that the gut microbiota’s inhibitory effects on Plasmodium outweigh the beneficial effects.

Bruce MC, Donnelly CA, Alpers MP, Galinski MR, Barnwell JW, Walliker D, Day KP, 2000, ‘Cross-species interactions between malaria parasites in humans.’, Science, 287(5454), pp 845-8, viewed on 6th August 2019, <https://www.ncbi.nlm.nih.gov/pubmed/10657296>
Romoli O, Gendrin M, 2018, ‘The Tripartite interactions between the mosquito, its microbiota and Plasmodium’, Parasites & Vectors, 11(1), viewed on 6th August 2019, <https://www.ncbi.nlm.nih.gov/pubmed/29558973>
Yilmaz B, Portugal S, Tran TM, Gozzelino R1, Ramos S, Gomes J, Regalado A, Cowan PJ, d’Apice AJ, Chong AS, Doumbo OK, Traore B, Crompton PD, Silveira H, Soares MP, 2014, ‘Gut microbiota elicits a protective immune response against malaria transmission’, Cell, 159(6), viewed on 6th August 2019, <https://www.ncbi.nlm.nih.gov/pubmed/25480293>